Lab clue into catastrophic drug trial

NINE months after six healthy young men nearly died during the trial of an experimental antibody in the UK, the dramatic changes to their immune system have been recreated in the lab – which seems to explain why the effects only showed up in humans and not in animals given the antibody.

The six suffered multiple organ failure after being injected with TGN1412, an antibody developed by the now bankrupt German company TeGenero at Northwick Park Hospital in London, on 13 March. The antibody was meant to calm the immune system. Instead, the men’s immune systems went into overdrive, attacking their internal organs. This hadn’t happened in tests on human cells or in macaque monkeys, which had received 500 times as much antibody as the men.

Stephen Inglis of the National Institute for Biological Standards and Control in Potters Bar, near London, now thinks he understands why. Preliminary results reveal that TGN1412 only sends human white blood cells berserk when “tethered” to a physical surface such as the base of a lab dish or in a layer of cells, as you would find in the organs of the body. The antibody had previously been tested on human cells only in solution, where it failed to produce this effect.

The antibody only drives human white blood cells berserk if it is tethered

Crucially, when macaque cells replaced the human cells the tethering had no effect, suggesting that the response is unique to humans – and explaining why the monkeys in the original trials didn’t get sick.

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